We plan to continue the isolation of pure fractions of fragmented sarcoplasmic reticulum, lysosomes and sarcolemma using a high-speed zonal rotor. The lipid composition of the pure lysosomes and sarcolemma will be estimated. Pre-treatment of animals with Verapamil will be done prior to isolation of organelles to allow assay of enzymes and Ca ion uptake that would be expected to be impaired by the progress of the cardiomyopathy. The contribution of the sympathetic nervous system to the development of the cardiomyopathy will be studied. Baseline turnover studies in normal, hypertrophic and failing hearts will allow comparisons of the efficacy of pharmacological interventions. Furthermore, the interrelationship of changes in levels of myocardial calcium and catecholamines will be pursued. Correlation of these changes with altered function of subcellular organelles will be investigated whenever possible.